Abstract
We previously described a model of polarized Th1 cell‐mediated anamnestic pulmonary granulomatous inflammation in sensitized mice induced by pulmonary embolization of agarose beads coated with covalently bound antigens of Mycobacteria bovis purified protein derivative (PPD). We have also demonstrated TLR9 plays an important role in maintaining the appropriate phenotype in a Th1 granulomatous response. We demonstrate in this study that TLR9−/− mice showed greatly increased granuloma formation as assessed by impaired myeloid dendritic cells and increased regulatory T cells, and Th‐2 skewed cytokine profile compared with wild‐type. Moreover, the expression of Th17 cytokine family members (IL‐17 and IL‐21) was abrogated in TLR9−/− mice. These data also support the concept that dendritic cells, but not macrophages, from bone marrow can promote the differentiation of Th‐17 cells, while both macrophages and dendritic cells promote Th‐1 cell differentiation after BCG stimulation. These findings support the concept that the impaired recruitment of granuloma dendritic cells alters the Th17 cytokine profile in TLR9‐deficient mice.This work was supported by NIH grants HL031963, HL074024, and HL031237.
Published Version
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